Is it safe to take lorazepam (Ativan) and clonazepam (Klonopin) together?

Concurrent Use of Lorazepam and Clonazepam

Taking lorazepam and clonazepam together is generally unsafe and should be avoided due to additive central nervous system depression, increased risk of respiratory depression, excessive sedation, falls, and cognitive impairment. 1, 2

Primary Safety Concerns

The combination of two benzodiazepines creates compounding risks:

• Respiratory depression is significantly amplified when benzodiazepines are combined with other CNS depressants, with studies showing hypoxemia rates increasing from 0% with single agents to 92% with combinations, and apnea occurring in 50% of subjects receiving dual CNS depressants 1
• Excessive sedation and cognitive impairment are predictable consequences, as both medications act on the same GABA-A receptor system 1, 3
• Fall risk is substantially elevated, particularly in elderly patients, when combining benzodiazepines 2, 3
• Paradoxical reactions including behavioral disinhibition can occur, especially in younger children and those with developmental disabilities 1

Clinical Context Where Dual Benzodiazepines May Occur

While generally contraindicated, there are rare scenarios where this combination might be encountered:

• Acute seizure management: Both lorazepam (duration up to 72 hours) and clonazepam (duration 24 hours) are used for status epilepticus, though typically not simultaneously 4, 5
• Transitioning between benzodiazepines: During cross-tapering when switching from one agent to another for chronic anxiety or seizure disorders 6
• Acute agitation in psychiatric emergencies: Combinations of benzodiazepines with antipsychotics have been studied, though combining two benzodiazepines is not standard practice 1

Pharmacologic Considerations

Both medications have overlapping but distinct properties:

• Lorazepam has intermediate action with duration up to 72 hours and higher receptor affinity, making it effective for acute anxiety and seizures 4, 6
• Clonazepam has longer duration (24 hours) and is used for panic disorder, seizure prophylaxis, and chronic anxiety 4, 6
• Additive effects occur because both enhance GABA-A receptor activity, creating synergistic CNS depression 1

Management Recommendations When Combination is Considered

If clinical circumstances absolutely require both medications (which should be exceedingly rare):

• Use the lowest effective doses of each agent, such as lorazepam 0.25-0.5 mg with clonazepam 0.25-0.5 mg maximum 1, 3
• Monitor continuously for respiratory depression, excessive sedation, confusion, and fall risk 2, 3
• Avoid in high-risk populations including elderly patients, those with respiratory compromise (COPD, asthma, sleep apnea), hepatic impairment, or myasthenia gravis 2, 3
• Involve multidisciplinary team including pharmacy and psychiatry to justify and monitor the combination 7, 3
• Document clear rationale in the medical record with specific treatment goals and timeline 7

Safer Alternatives

Rather than combining benzodiazepines:

• Optimize single benzodiazepine dosing: Adjust the dose or timing of one agent before adding a second 7
• Consider non-benzodiazepine anxiolytics: SSRIs, SNRIs, buspirone, or hydroxyzine as first-line options for anxiety 7
• Use appropriate agent for indication: Choose lorazepam for acute anxiety/agitation or clonazepam for panic disorder, but not both simultaneously 6, 8

Discontinuation Strategy

If a patient is already taking both medications:

• Taper gradually: Reduce by 25% every 1-2 weeks to avoid withdrawal symptoms including rebound anxiety, seizures, and delirium 7, 2
• Consolidate to single agent first: Transition to the more appropriate benzodiazepine for the patient's condition before tapering 7
• Monitor for withdrawal: Watch for anxiety, insomnia, tremor, seizures, and autonomic instability during taper 7, 2

Critical Pitfalls to Avoid

• Never prescribe pro re nata (PRN) combinations of two benzodiazepines, as this is explicitly prohibited 1
• Do not underestimate additive sedation especially in elderly or medically compromised patients 2, 3
• Avoid in patients with contraindications including severe pulmonary insufficiency, severe liver disease, or concurrent use of other CNS depressants 3
• Do not combine with opioids: This creates a 3- to 10-fold increase in mortality risk from respiratory depression 7